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Zvidzidzo zvakawanda zvemetabolism mumakonzo zvinoitwa patembiricha yekamuri, kunyangwe pasi pemamiriro aya, kusiyana nevanhu, mbeva dzinoshandisa simba rakawanda kuchengetedza tembiricha yemukati.Pano, tinotsanangura uremu hwakajairika uye kufutisa-kunokonzerwa nekudya (DIO) muC57BL / 6J mbeva dzakadyiswa chow chow kana 45% kudya kwemafuta akawanda, zvichiteerana.Mice dzakaiswa kwemazuva 33 pa22, 25, 27.5 uye 30 ° C. mune imwe nzira isina kunanga calorimetry.Tinoratidza kuti kushandiswa kwesimba kunowedzera zvakatevedzana kubva pa30°C kusvika pa22°C uye kunosvika 30% kukwira pa22°C mumamodheru ese ari maviri.Mune huremu hwakajairika mbeva, kudya kwekudya kwaipokana neEE.Sezvineiwo, DIO mbeva hadzina kuderedza kudya apo EE yakadzikira.Nokudaro, pakupera kwechidzidzo, mice pa 30 ° C yakanga ine uremu hwepamusoro, mafuta akawanda uye plasma glycerol uye triglycerides kupfuura mice pa 22 ° C.Iko kusaenzana muDIO mbeva kunogona kunge kuri nekuda kwekuwedzera mafaro-kwakavakirwa kudya.
Mbeva ndiyo inonyanya kushandiswa mhando yemhuka pakudzidza physiology yemunhu uye pathophysiology, uye kazhinji ndiyo mhuka yakasarudzika inoshandiswa mumatanho ekutanga ekuwanikwa kwezvinodhaka nekusimudzira.Nekudaro, mbeva dzinosiyana nevanhu munzira dzakati wandei dzakakosha dzemuviri, uye nepo allometric scaling inogona kushandiswa kune imwe nhanho kuturikira muvanhu, misiyano mikuru pakati pembeva nevanhu iri muthermoregulation uye simba homeostasis.Izvi zvinoratidza kusawirirana kwakakosha.Avhareji yemuviri wembeva dzakura dzinenge dzine chiuru zvishoma pane dzevakuru (50 g vs. 50 kg), uye nzvimbo yepamusoro kune huwandu hwehuwandu hunosiyana neine 400 nguva nekuda kwekusava nemutsara wejometri shanduko inotsanangurwa naMee. .Equation 2. Nekuda kweizvozvo, mbeva dzinorasikirwa zvakanyanya nekupisa kunoenderana nehuwandu hwadzo, saka dzinonyanya kunzwa tembiricha, dzinowanzoita hypothermia, uye dzine avhareji yebasal metabolic rate yakapetwa kagumi kupfuura yevanhu.Patembiricha yekamuri (~ 22°C), mbeva dzinofanira kuwedzera simba radzo rose rekushandisa (EE) nechikamu che30% kuchengetedza tembiricha yemuviri.Pakutonhora kwakadzika, EE inowedzera zvakanyanya ne50% uye 100% pa15 ne7°C zvichienzaniswa neEE pa22°C.Nekudaro, mamiriro edzimba akajairwa anokonzeresa kutonhora kwekushushikana, izvo zvinogona kukanganisa kuchinjika kwembeva mhedzisiro kuvanhu, sezvo vanhu vanogara munharaunda dzemazuva ano vanopedza yakawanda yenguva yavo mu thermoneutral mamiriro (nekuti nzvimbo yedu yepasi reshiyo inotarisana nevhoriyamu inoita kuti tisanyanya kunzwira tsitsi. tembiricha, sezvo isu tichigadzira iyo thermoneutral zone (TNZ) yakatitenderedza EE pamusoro pebasal metabolic rate) inosvika ~ 19 kusvika 30 ° C6, nepo mbeva dzine bhendi rakakwirira uye rakatetepa rinotenderera chete 2-4 ° C7,8 Muchokwadi, ichi chakakosha. chikamu chakatariswa zvakanyanya mumakore achangopfuura 4, 7,8,9,10,11,12 uye zvave zvataurwa kuti mamwe "misiyano yemhando" inogona kudzikiswa nekuwedzera tembiricha yegoko 9. Zvisineyi, hapana kubvumirana pane tembiricha. izvo zvinoumba thermoneutrality mumakonzo.Nokudaro, kana iyo yakaderera yekushisa kwekushisa mu thermoneutral range mumagumbo ega-mabvi iri pedyo ne25 ° C kana pedyo ne30 ° C4, 7, 8, 10, 12 inoramba ichikakavadzana.EE uye mamwe ma metabolic ma parameter akaganhurirwa kumaawa kusvika kumazuva, saka mwero wekuti kuratidzwa kwenguva refu kune akasiyana tembiricha kunogona kukanganisa metabolic paramita sehuremu hwemuviri hauna kujeka.kushandiswa, kushandiswa kwe substrate, kushivirira kweglucose, uye plasma lipid uye glucose concentrations uye chido-chinodzora mahomoni.Pamusoro pezvo, kumwe kutsvagurudza kunodiwa kuti uone kuti kudya kungaita sei maparamendi aya (DIO mbeva pakudya kwemafuta akawandisa angave akananga kune mafaro-based (hedonic) chikafu).Kuti tipe rumwe ruzivo nezvenyaya iyi, takaongorora maitiro ekurera tembiricha pane ambotaurwa metabolic paramita mune akajairwa-huremu hwechirume mbeva uye kudya-induced obese (DIO) mbeva dzechirume pane 45% yakakwira-mafuta kudya.Mbeva dzakachengetwa pa22, 25, 27.5, kana 30 ° C kwemavhiki matatu.Tembiricha dziri pasi pe22°C hadzina kudzidzwa nekuti magariro emhuka haawanzo kudzika pasi tembiricha yemumba.Takaona kuti zvakajairwa-huremu uye imwechete-denderedzwa DIO mbeva dzakapindura zvakafanana kune shanduko yekuvharirwa tembiricha maererano neEE uye zvisinei neyakavharirwa mamiriro (ine kana isina pekugara / nesting zvinhu).Nekudaro, nepo mbeva dzehuremu dzakajairwa dzakagadzirisa kudya kwavo maererano neEE, kudya kweDIO mbeva kwainyanya kuzvimiririra paEE, zvichikonzera kuti mbeva dziwedzere huremu.Zvinoenderana nedata rehuremu hwemuviri, kuwanda kweplasma yelipids uye miviri yeketone yakaratidza kuti DIO mbeva pa30 ° C yaive neyakagwinya simba chiyero kupfuura mbeva pa22 ° C.Zvikonzero zvinokonzeresa mutsauko mukuyerwa kwesimba rekutora uye EE pakati pehuremu hwakajairika uye DIO mbeva zvinoda kumwe kudzidza, asi zvinogona kunge zvine chekuita nekuchinja kwepathophysiological muDIO mbeva uye mhedzisiro yekunakidzwa-kwakavakirwa kudya semhedzisiro yekudya kwakakora.
EE yakawedzera mutsara kubva pa30 kusvika 22 ° C uye yakanga inenge 30% yakakwirira pa22 ° C kana ichienzaniswa ne30 ° C (Fig. 1a, b).Chiyero chekutsinhanisa chekufema (RER) chaive chakazvimirira pane tembiricha (Fig. 1c, d).Kudya kwekudya kwaienderana neEE dynamics uye kwakawedzera nekuderera kwekushisa (uyewo ~ 30% yakakwirira pa22 ° C kana ichienzaniswa ne30 ° C (Fig. 1e, f) Kutora mvura. 1g).
Mice yevarume (C57BL / 6J, mavhiki e20, imba yega yega, n = 7) yakachengetwa mumakeji emagetsi pa 22 ° C. kwevhiki imwe isati yatanga kudzidza.Mazuva maviri mushure mekuunganidzwa kwe data kumashure, tembiricha yakasimudzwa mu2 ° C increments pa 06:00 maawa pazuva (kutanga kwechikamu chechiedza).Dhata dzinounzwa sezvinoreva ± chiyero chikanganiso chezvinoreva, uye chikamu cherima (18:00–06:00 h) chinomiririrwa nebhokisi regrey.a Energy expenditure (kcal/h), b Total simba rekushandisa patembiricha dzakasiyana (kcal/24 h), c Respiratory exchange rate (VCO2/VO2: 0.7–1.0), d Zvinoreva RER muchiedza nerima (VCO2 /VO2) chikamu (zero kukosha kunotsanangurwa se 0.7).e kuwanda kwekudya kwekudya (g), f 24h yakazara yekudya, g 24h yakazara yemvura yekunwa (ml), h 24h yakazara yemvura yekunwa, i cumulative chiitiko nhanho (m) uye j yakazara chiitiko chenhanho (m/24h) .).Mbeva dzakachengetwa patembiricha yairatidzwa kwemaawa makumi mana nemasere.Data yakaratidzwa ye24, 26, 28 uye 30 ° C inoreva maawa makumi maviri nemana ekupedzisira ekutenderera kwega.Mbeva dzakaramba dzakadyiswa mukati mekudzidza.Kukosha kwenhamba kwakaedzwa nekudzokororwa kuyerwa kwenzira imwe ANOVA ichiteverwa neTukey's multiple comparison test.Asterisks inoratidza kukosha kwekutanga kukosha kwe22 ° C, shading inoratidza kukosha pakati pemamwe mapoka sezvakaratidzwa. *P <0.05, **P <0.01, **P <0.001, ****P <0.0001. *P <0.05, **P <0.01, **P <0.001, ****P <0.0001. *P <0,05, **P <0,01, **P <0,001, ****P <0,0001. *P<0.05, **P<0.01, **P<0.001, ****P<0.0001. *P <0.05,**P <0.01,**P <0.001,****P <0.0001. *P <0.05,**P <0.01,**P <0.001,****P <0.0001. *P <0,05, **P <0,01, **P <0,001, ****P <0,0001. *P<0.05, **P<0.01, **P<0.001, ****P<0.0001.Avhareji tsika dzakaverengerwa kwenguva yese yekuyedza (0-192 maawa).n = 7.
Sezvakaitika pamakonzo ehuremu hwemazuva ose, EE yakawedzera mutsara nekuderera kwekushisa, uye munyaya iyi, EE yaivawo inenge 30% yakakwirira pa22 ° C kana ichienzaniswa ne30 ° C (Fig. 2a, b).RER haina kuchinja pakupisa kwakasiyana (Fig. 2c, d).Kusiyana nemakonzo akajairwa uremu, kudya kwekudya kwaisaenderana neEE sebasa rekushisa kwekamuri.Kudya kwekudya, kunwa kwemvura, uye nhanho yebasa zvaive zvakasununguka kubva kune tembiricha (Fig. 2e-j).
Murume (C57BL / 6J, mavhiki e20) DIO mbeva dzaive dzakachengetwa mumakamuri emagetsi pa 22 ° C. kwevhiki imwe isati yatanga chidzidzo.Mbeva dzinogona kushandisa 45% HFD ad libitum.Mushure mekugadzirisa kwemazuva maviri, data yekutanga yakaunganidzwa.Zvadaro, tembiricha yakasimudzwa mukuwedzera kwe2°C mamwe mazuva na06:00 (kutanga kwechikamu chechiedza).Dhata dzinounzwa sezvinoreva ± chiyero chikanganiso chezvinoreva, uye chikamu cherima (18:00–06:00 h) chinomiririrwa nebhokisi regrey.a Energy expenditure (kcal/h), b Total simba rekushandisa patembiricha dzakasiyana (kcal/24 h), c Respiratory exchange rate (VCO2/VO2: 0.7–1.0), d Zvinoreva RER muchiedza nerima (VCO2 /VO2) chikamu (zero kukosha kunotsanangurwa se 0.7).e kuwanda kwekudya kwekudya (g), f 24h yakazara yekudya, g 24h yakazara yemvura yekunwa (ml), h 24h yakazara yemvura yekunwa, i cumulative chiitiko nhanho (m) uye j yakazara chiitiko chenhanho (m/24h) .).Mbeva dzakachengetwa patembiricha yairatidzwa kwemaawa makumi mana nemasere.Data yakaratidzwa ye24, 26, 28 uye 30 ° C inoreva maawa makumi maviri nemana ekupedzisira ekutenderera kwega.Mbeva dzakachengetwa pa45% HFD kusvika pakupera kwechidzidzo.Kukosha kwenhamba kwakaedzwa nekudzokororwa kuyerwa kwenzira imwe ANOVA ichiteverwa neTukey's multiple comparison test.Asterisks inoratidza kukosha kwekutanga kukosha kwe22 ° C, shading inoratidza kukosha pakati pemamwe mapoka sezvakaratidzwa. *P <0.05, ***P <0.001, ****P <0.0001. *P <0.05, ***P <0.001, ****P <0.0001. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001. *P <0.05,***P <0.001,****P <0.0001. *P <0.05,***P <0.001,****P <0.0001. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001.Avhareji tsika dzakaverengerwa kwenguva yese yekuyedza (0-192 maawa).n = 7.
Mune imwe nhevedzano yezviedzo, takaongorora mabatiro etembiricha yakadzika pamaparamita mamwe chete, asi panguva ino pakati pemapoka emakonzo aigara akachengetwa pane imwe tembiricha.Mbeva dzakakamurwa kuita mapoka mana kuti kuderedze shanduko yenhamba mune inorehwa uye chiyero kutsauka kwehuremu hwemuviri, mafuta, uye yakajairika uremu hwemuviri (Fig. 3a-c).Mushure memazuva manomwe ekugadzirisa, mazuva 4.5 eEE akanyorwa.EE inobatwa zvakanyanya neambient tembiricha panguva yemasikati uye husiku (Fig. 3d), uye inowedzera mutsara sezvo tembiricha inoderera kubva pa27.5 ° C kusvika 22 ° C (Fig. 3e).Kuenzaniswa nemamwe mapoka, RER yeboka re25 ° C yakaderedzwa, uye pakanga pasina misiyano pakati pemapoka akasara (Fig. 3f, g).Kudya kwekudya kwakafanana neEE pattern yakawedzera neinenge 30% pa22 ° C zvichienzaniswa ne30 ° C (Fig. 3h, i).Kushandiswa kwemvura uye maitiro ekuita haana kusiyana zvakanyanya pakati pemapoka (Fig. 3j, k).Kuratidzwa kwekushisa kwakasiyana-siyana kwemazuva anosvika makumi matatu nematatu hakuna kutungamirira kune kusiyana kwehuremu hwemuviri, kuonda, uye mafuta akawanda pakati pemapoka (Fig. 3n-s), asi zvakakonzera kuderera kwemuviri wakaonda weanenge 15% kana ichienzaniswa ne zvibodzwa zvekuzvizivisa (Fig. 3n-s).3b, r, c)) uye mafuta akawanda akawedzera nekanopfuura ka2 (kubva ~ 1 g kusvika 2-3 g, Fig. 3c, t, c).Sezvineiwo, iyo 30°C kabati ine zvikanganiso zvekugadzirisa uye haigone kupa data reEE neRER rakarurama.
- Huremu hwemuviri (a), huremu hwakaonda (b) uye huwandu hwemafuta (c) mushure memazuva masere (zuva rimwe chete risati raendeswa kuSABLE system).d Kushandiswa kwesimba (kcal / h).e Avhareji yekushandiswa kwesimba (0-108 maawa) pakupisa kwakasiyana-siyana (kcal / 24 maawa).f Respiratory exchange ratio (RER) (VCO2/VO2).g Kureva RER (VCO2/VO2).h Kuwanda kwekudya kwekudya (g).i Kureva kudya kwekudya (g/24 maawa).j Kushandiswa kwemvura yose (ml).k Avhareji yekushandisa mvura (ml/24 h).l Cumulative chiitiko level (m).m Avhareji yezinga rekuita (m/24 h).n huremu hwemuviri pazuva regumi nemasere, o kuchinja kwehuremu hwemuviri (kubva pa -8 kusvika kuzuva re18), huremu huremu pazuva regumi nemasere, q kushanduka kwehuremu (kubva -8 kusvika 18 zuva), r mafuta mashoma pazuva regumi nesere. , uye kuchinja muhuwandu hwemafuta (kubva -8 kusvika ku18 mazuva).Kukosha kwehuwandu hwematanho akadzokororwa akaedzwa neOneway-ANOVA ichiteverwa neTukey's multiple comparison test. *P < 0.05, **P < 0.01, ***P <0.001, ****P <0.0001. *P < 0.05, **P < 0.01, ***P <0.001, ****P <0.0001. *P <0,05, **P <0,01, ***P <0,001, ****P <0,0001. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001. *P <0.05,**P <0.01,***P <0.001,****P <0.0001. *P <0.05,**P <0.01,***P <0.001,****P <0.0001. *P <0,05, **P <0,01, ***P <0,001, ****P <0,0001. *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.Dhata dzinounzwa sezvinoreva + chiyero chikanganiso chezvinoreva, chikamu cherima (18:00-06:00 h) chinomiririrwa negrey mabhokisi.Madotsi ari pahistograms anomiririra mbeva.Avhareji tsika dzakaverengerwa kwenguva yese yekuyedza (0-108 maawa).n = 7.
Mice dzaive dzakafananidzwa muhuremu hwemuviri, huremu hwakaonda, uye huwandu hwemafuta panguva yekutanga (Figs. 4a-c) uye yakachengetedzwa pa22, 25, 27.5, uye 30 ° C sezviri muzvidzidzo nemararamiro ehuremu..Kana tichienzanisa mapoka emakonzo, hukama pakati peEE uye tembiricha yakaratidza hukama hwakafanana hwemutsara nekupisa nekufamba kwenguva mumakonzo mamwe.Nokudaro, mbeva dzakachengetwa pa22 ° C dzakapedza simba rinenge 30% kupfuura mbeva dzakachengetwa pa30 ° C (Fig. 4d, e).Paunenge uchidzidza mhedzisiro mumhuka, tembiricha haina kugara ichikanganisa RER (Fig. 4f, g).Kudya kwekudya, kunwa mvura, uye basa hazvina kunyanya kukanganiswa nekushisa (Fig. 4h-m).Mushure memazuva makumi matatu nematatu ekurerwa, mbeva pa 30 ° C dzaive nehuremu hwemuviri hwakanyanya kudarika mbeva pa22 ° C (Fig. 4n).Zvichienzaniswa nemapoinzi avo ekutanga, mbeva dzakarererwa pa30 ° C dzaive nehuremu hwemuviri hwakanyanya kupfuura mbeva dzakarerwa pa22 ° C (kureva ± kukanganisa kwakajairwa kwezvinoreva: Fig. 4o).Kuwedzera kwehuremu hwepamusoro hwakakonzerwa nekuwedzera kwehuwandu hwemafuta (Fig. 4p, q) panzvimbo yekuwedzera kwemaonda (Fig. 4r, s).Zvichienderana nechepasi EE kukosha pa 30 ° C, kutaura kwemarudzi akawanda eBAT anowedzera BAT basa / basa rakaderedzwa pa 30 ° C zvichienzaniswa ne 22 ° C: Adra1a, Adrb3, uye Prdm16.Mamwe majini akakosha anowedzerawo BAT basa / chiitiko haana kukanganiswa: Sema3a (neurite kukura mutemo), Tfam (mitochondrial biogenesis), Adrb1, Adra2a, Pck1 (gluconeogenesis) uye Cpt1a.Zvinoshamisa kuti, Ucp1 uye Vegf-a, yakabatana nekuwedzera thermogenic basa, haina kuderera muboka re30 ° C.Muchokwadi, mazinga eUcp1 mumakonzo matatu aive akakwira kupfuura muboka re22 ° C, uye Vegf-a neAdrb2 zvakasimudzwa zvakanyanya.Kuenzaniswa neboka re22 ° C, mbeva dzakachengetwa pa25 ° C uye 27.5 ° C dzakaratidza kusachinja (Supplementary Figure 1).
- Huremu hwemuviri (a), huremu hwakaonda (b) uye huwandu hwemafuta (c) mushure memazuva 9 (zuva rimwe risati raendeswa kuSABLE system).d Kushandiswa kwesimba (EE, kcal / h).e Avhareji yekushandiswa kwesimba (0-96 maawa) pakupisa kwakasiyana-siyana (kcal / 24 maawa).f Respiratory exchange ratio (RER, VCO2/VO2).g Kureva RER (VCO2/VO2).h Kuwanda kwekudya kwekudya (g).i Kureva kudya kwekudya (g/24 maawa).j Kushandiswa kwemvura yose (ml).k Avhareji yekushandisa mvura (ml/24 h).l Cumulative chiitiko level (m).m Avhareji yezinga rekuita (m/24 h).n Huremu hwemuviri pazuva 23 (g), o Shanduko yehuremu hwemuviri, p Huremu hwakaonda, q Shanduko yehuremu hwakaonda (g) pazuva 23 zvichienzaniswa nezuva 9, Shanduko muhuremu hwemafuta (g) pa23 -day, mafuta uremu (g) zvichienzaniswa nezuva 8, zuva 23 zvichienzaniswa -8th zuva.Kukosha kwehuwandu hwematanho akadzokororwa akaedzwa neOneway-ANOVA ichiteverwa neTukey's multiple comparison test. *P <0.05, ***P <0.001, ****P <0.0001. *P <0.05, ***P <0.001, ****P <0.0001. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001. *P <0.05,***P <0.001,****P <0.0001. *P <0.05,***P <0.001,****P <0.0001. *Р<0,05, ***Р<0,001, ****Р<0,0001. *P<0.05, ***P<0.001, ****P<0.0001.Dhata dzinounzwa sezvinoreva + chiyero chikanganiso chezvinoreva, chikamu cherima (18:00-06:00 h) chinomiririrwa negrey mabhokisi.Madotsi ari pahistograms anomiririra mbeva.Mean values akaverengerwa kwenguva yese yekuyedza (0-96 maawa).n = 7.
Kufanana nevanhu, mbeva dzinowanzogadzira nharaunda kuti dzideredze kurasikirwa kwekupisa kune zvakatipoteredza.Kuti tione kukosha kwenzvimbo iyi yeEE, takaongorora EE pa22, 25, 27.5, uye 30 ° C, iine kana isina magadhi ematehwe uye nesting material.Pa22 ° C, kuwedzerwa kwematehwe akajairwa kunoderedza EE ne4%.Kuwedzerwa kwakatevera kwezvinhu zvekugara kwakaderedza EE ne3-4% (Fig. 5a, b).Hapana kuchinja kwakakosha muRER, kudya kwekudya, kunwa kwemvura, kana mazinga emabasa akaonekwa nekuwedzera kwedzimba kana matehwe + mabhedha (Mufananidzo 5i-p).Kuwedzerwa kweganda uye nesting material zvakare yakaderedza zvakanyanya EE pa25 uye 30 ° C, asi mhinduro dzaive shoma.Pa27.5 ° C hapana mutsauko wakaonekwa.Zvinonzwisisika, mukuedza uku, EE yakaderera nekuwedzera kwekushisa, munyaya iyi inenge 57% yakaderera pane EE pa30 ° C ichienzaniswa ne22 ° C (Fig. 5c-h).Kuongorora kwakafanana kwakaitwa chete nokuda kwechikamu chechiedza, apo EE yakanga iri pedyo nechiyero chekugadzirisa metabolic, sezvo munyaya iyi mbeva dzainyanya kuzorora paganda, zvichiita kuti kuenzanisa kwemaitiro kuenzane nekupisa kwakasiyana (Supplementary Fig. 2a-h) .
Dhata yemakonzo kubva pekugara uye nesting zvinhu (yakasviba bhuruu), imba asi isina nesting zvinhu (chiedza chebhuruu), uye imba uye nest zvinhu (orenji).Kushandiswa kwesimba (EE, kcal/h) kumakamuri a, c, e uye g pa22, 25, 27.5 uye 30 °C, b, d, f uye h zvinoreva EE (kcal/h).ip Data yemakonzo akachengetwa pa22°C: i reresheni yekufema (RER, VCO2/VO2), j kureva RER (VCO2/VO2), k kuwedzera kwechikafu kudyiwa (g), l avhareji yekudya (g/24 h), m kunwa kwese kwemvura (mL), n avhareji yemvura yekunwa AUC (mL/24h), o yakazara chiitiko (m), p avhareji yenhanho yebasa (m/24h).Dhata dzinounzwa sezvinoreva + chiyero chikanganiso chezvinoreva, chikamu cherima (18:00-06:00 h) chinomiririrwa negrey mabhokisi.Madotsi ari pahistograms anomiririra mbeva.Kukosha kwehuwandu hwematanho akadzokororwa akaedzwa neOneway-ANOVA ichiteverwa neTukey's multiple comparison test. *P <0.05, **P <0.01. *P <0.05, **P <0.01. *Р<0,05, **Р<0,01. *P<0.05, **P<0.01. *P <0.05,**P <0.01. *P <0.05,**P <0.01. *Р<0,05, **Р<0,01. *P<0.05, **P<0.01.Avhareji tsika dzakaverengerwa kwenguva yese yekuyedza (0-72 maawa).n = 7.
Mumakonzo ehuremu hwemazuva ese (2-3 maawa ekutsanya), kurera pane tembiricha dzakasiyana hakuna kukonzeresa misiyano yakakura muplasma yakawandisa yeTG, 3-HB, cholesterol, ALT, uye AST, asi HDL sebasa rekushisa.Mufananidzo 6a-e).Kutsanya kweplasma kusanganiswa kweleptin, insulini, C-peptide, uye glucagon zvakare haina kusiyana pakati pemapoka (Mifananidzo 6g-j).Pazuva rekuedzwa kweglucose kushivirira (mushure memazuva makumi matatu nerimwe pakupisa kwakasiyana), chiyero chekutanga cheglucose yeropa (5-6 maawa ekutsanya) yaive inenge 6.5 mM, pasina mutsauko pakati pemapoka. Kutungamirirwa kweglucose yemuromo kwakawedzera kuwanda kweglucose yeropa zvakanyanya mumapoka ose, asi zvose zviri zviviri nzvimbo yepamusoro uye nzvimbo yekuwedzera pasi pemakona (iAUCs) (15-120 min) yakanga yakaderera muboka remakonzo akachengetwa pa 30 ° C (nguva imwe neimwe: P <0.05–P <0.0001, Fig. 6k, l) zvichienzaniswa nemakonzo akachengetwa pa22, 25 uye 27.5 °C (iyo isina kusiyana pakati peumwe neumwe). Kutungamirirwa kweglucose yemuromo kwakawedzera kuwanda kweglucose yeropa zvakanyanya mumapoka ose, asi zvose zviri zviviri nzvimbo yepamusoro uye nzvimbo yekuwedzera pasi pemakona (iAUCs) (15-120 min) yakanga yakaderera muboka remakonzo akachengetwa pa 30 ° C (nguva imwe neimwe: P <0.05-P <0.0001, Fig. 6k, l) zvichienzaniswa nemakonzo akachengetwa pa22, 25 uye 27.5 °C (iyo isina kusiyana pakati peumwe neumwe). Пероральное введение значительно повышало концентрацию в крови во всех группах, но как пиковая концентраи, концентраи выми (iAUC) (15–120 мин) были ниже в группе мышей, содержащихся при 30 °C (отдельные временные точки: P < 0,05–P < 0,0001, рис 6k, l) по сравнению с мышами, содержащимися при 22, 25 и 27,5 ° C (которые не различались между). Oral administration yeglucose yakawedzera zvakanyanya kuwedzera kweglucose yeropa mumapoka ose, asi zvose zvepamusoro-soro uye nzvimbo yekuwedzera pasi pemakona (iAUC) (15-120 min) yakanga yakaderera muboka re 30 ° C mice (nguva yakasiyana: P <0.05- - P <0.0001, Fig. 6k, l) yakaenzaniswa nemakonzo akachengetwa pa22, 25 uye 27.5 ° C (iyo yakanga isina kusiyana kubva kune imwe neimwe).口服葡萄糖的给药显着增加了所有组的血糖浓度，但在30 °C 饲养的小鼠组中，峰值浓度和时候(1) -120 分钟) 均较低（各个时间点:P <0.05–P <0.0001,图6k,l）与饲养在22,25 and27.5°C 的小鼠（彼此之间有差异）相比。口服 葡萄糖 的 给 药 显着 了 所有组 的 血糖 浓度 但 在 30 ° C 饲养 小鼠组 中度 ，积 面积 (IAUC) (15-120 分钟) 均 较 低 各 个 点 点 点点点:P < 0.05–P < 0.0001, 图6k,l）与饲养在22,25和27.5°C 的小鼠（彼此之间沒有差弸毉盉。Oral administration yeglucose yakawedzera zvakanyanya kuwedzera kweglucose yeropa mumapoka ose, asi zvose zvepamusoro-soro uye nzvimbo iri pasi pevhavha (iAUC) (15-120 min) yakanga yakaderera mu30 ° C-yakadyiswa mbeva boka (nguva dzose dzenguva).: P <0,05–P <0,0001, рис. : P <0.05–P <0.0001, Fig.6l, l) zvichienzaniswa nemakonzo akachengetwa pa22, 25 uye 27.5 ° C (hapana mutsauko kubva kune mumwe).
Plasma concentrations yeTG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulini, C-peptide, uye glucagon inoratidzwa muvarume vakuru DIO (al) mbeva mushure memazuva makumi matatu nematatu ekudyisa pane yakaratidzwa tembiricha. .Mice hadzina kudyiswa 2-3 maawa asati atorwa ropa.Kusarudzika yaive yemuromo glucose kushivirira bvunzo, iyo yakaitwa mazuva maviri isati yapera chidzidzo pamakonzo akatsanya kwemaawa 5-6 uye akachengetwa panguva yakakodzera tembiricha kwemazuva makumi matatu nerimwe.Mbeva dzakapikiswa ne 2 g/kg uremu hwemuviri.Iyo nharaunda iri pasi peiyo curve data (L) inoratidzirwa sekuwedzera data (iAUC).Data inoratidzwa sezvinoreva ± SEM.Madotsi anomiririra sampuli dzega. *P <0.05, **P <0.01, **P <0.001, ****P <0.0001, n = 7. *P <0.05, **P <0.01, **P <0.001, ****P <0.0001, n = 7. *P <0,05, **P <0,01, **P <0,001, ****P <0,0001, n = 7. *P<0.05, **P<0.01, **P<0.001, ****P<0.0001, n=7. *P <0.05,**P <0.01,**P <0.001,****P <0.0001,n = 7. *P <0.05,**P <0.01,**P <0.001,****P <0.0001,n = 7. *P <0,05, **P <0,01, **P <0,001, ****P <0,0001, n = 7. *P<0.05, **P<0.01, **P<0.001, ****P<0.0001, n=7.
MuDIO mice (zvakare yakatsanya kwemaawa 2-3), plasma cholesterol, HDL, ALT, AST, uye FFA concentrations haina kusiyana pakati pemapoka.Zvose TG uye glycerol zvakasimudzwa zvakanyanya muboka re30 ° C zvichienzaniswa neboka re22 ° C (Mifananidzo 7a-h).Kusiyana neizvi, 3-GB yakanga inenge 25% yakaderera pa30 ° C ichienzaniswa ne22 ° C (Mufananidzo 7b).Nokudaro, kunyange zvazvo mbeva dzakachengetwa pa22 ° C dzakanga dzine simba rose rakanaka, sezvinoratidzwa nekurema, kusiyana kweplasma yeTG, glycerol, uye 3-HB inoratidza kuti mbeva pa 22 ° C apo sampling yakanga iri pasi pe22 °. C.°C.Mbeva dzakakurira pa30 ° C dzaive muchimiro chine simba.Zvichienderana neizvi, kuwedzera kwechiropa cheglycerol uye TG, asi kwete glycogen uye cholesterol, yakanga yakakwirira muboka re30 ° C (Supplementary Fig. 3a-d).Kuti tiongorore kana kusiyana kwekushisa-kunoenderana ne lipolysis (sekuyerwa neplasma TG uye glycerol) mhedzisiro yekuchinja kwemukati mu epididymal kana inguinal mafuta, takabvisa adipose tishu kubva muzvitoro izvi pakupera kwechidzidzo uye quantified free fatty acid ex. vivo.uye kusunungurwa kweglycerol.Mumapoka ose ekuedza, adipose tissue samples kubva epididymal uye inguinal depots akaratidza kanenge kaviri kuwedzera kweglycerol uye FFA kugadzirwa mukupindura isoproterenol stimulation (Supplementary Fig. 4a-d).Zvisinei, hapana mhedzisiro yekushisa kwegomba pane basal kana isoproterenol-stimulated lipolysis yakawanikwa.Zvichienderana nehuremu hwemuviri uye huwandu hwemafuta, mazinga eplasma leptin aive akakwirira zvakanyanya muboka re30 ° C kupfuura muboka re22 ° C (Mufananidzo 7i).Pane zvinopesana, mazinga eplasma e insulin neC-peptide haana kusiyana pakati pemapoka ekushisa (Fig. 7k, k), asi plasma glucagon yakaratidza kuvimba nekushisa, asi munyaya iyi inenge 22 ° C muboka rakatarisana rakaenzaniswa kaviri. kusvika 30°C.KUBVA.Boka C (Mufananidzo 7l).FGF21 haina kusiyana pakati pemapoka akasiyana ekushisa (Fig. 7m).Pazuva reOGTT, yekutanga glucose yeropa yaiva inenge 10 mM uye haina kusiyana pakati pemakonzo akachengetwa pane zvakasiyana-siyana zvekushisa (Fig. 7n).Kudzorwa nemuromo kweglucose kwakawedzera mazinga eglucose eropa uye kwakakwira mumapoka ese pakusangana kweanenge 18 mM 15 maminetsi mushure mekutora.Pakanga pasina misiyano yakakosha muIAUC (15-120 min) uye kutariswa panguva dzakasiyana-siyana post-dose (15, 30, 60, 90 uye 120 min) (Mufananidzo 7n, o).
Plasma concentrations yeTG, 3-HB, cholesterol, HDL, ALT, AST, FFA, glycerol, leptin, insulini, C-peptide, glucagon, uye FGF21 yakaratidzwa muvarume vakuru DIO (ao) mice mushure memazuva 33 ekudya.tembiricha yakatarwa.Mice hadzina kudyiswa 2-3 maawa asati atorwa ropa.Oral glucose tolerance test yaive yakasarudzika sezvo yakaitwa pachiyero che 2 g / kg uremu hwemuviri mazuva maviri isati yapera chidzidzo mumakonzo akatsanya kwemaawa 5-6 uye akachengetwa panguva yakakodzera tembiricha kwemazuva makumi matatu nerimwe.Iyo nharaunda iri pasi peiyo curve data (o) inoratidzwa seyakawedzera data (iAUC).Data inoratidzwa sezvinoreva ± SEM.Madotsi anomiririra sampuli dzega. *P <0.05, **P <0.01, **P <0.001, ****P <0.0001, n = 7. *P <0.05, **P <0.01, **P <0.001, ****P <0.0001, n = 7. *P <0,05, **P <0,01, **P <0,001, ****P <0,0001, n = 7. *P<0.05, **P<0.01, **P<0.001, ****P<0.0001, n=7. *P <0.05,**P <0.01,**P <0.001,****P <0.0001,n = 7. *P <0.05,**P <0.01,**P <0.001,****P <0.0001,n = 7. *P <0,05, **P <0,01, **P <0,001, ****P <0,0001, n = 7. *P<0.05, **P<0.01, **P<0.001, ****P<0.0001, n=7.
Kufambiswa kwedhata regonzo kuvanhu inyaya yakaoma inoita basa repakati mukududzira kukosha kwekutarisa mumamiriro ekutsvaga kwephysiological uye pharmacological.Nekuda kwezvikonzero zvehupfumi uye kufambisa tsvagiridzo, mbeva dzinowanzo chengetwa pakamuri tembiricha pazasi penzvimbo yadzo ye thermoneutral, zvichikonzera kuvhurwa kweakasiyana-siyana anobhadhara physiological masisitimu ayo anowedzera mwero wemetabolism uye zvinogona kukanganisa kududzira9.Nokudaro, kuratidzwa kwemakonzo kutonhora kunogona kuita kuti mbeva dzirambe dzichiita kufutisa uye zvinogona kudzivirira hyperglycemia mumakonzo anorapwa ne streptozotocin nekuda kwekuwedzera kwekutakura kweglucose kusingaite insulin.Nekudaro, hazvina kujeka kuti kusvika papi kuratidzwa kwenguva yakareba kune akasiyana tembiricha akakodzera (kubva mukamuri kuenda kune thermoneutral) inokanganisa akasiyana simba homeostasis yeakajairwa uremu mbeva (pakudya) uye DIO mbeva (paHFD) uye metabolic paramita, pamwe nehukuru. kwavakakwanisa kuenzanisa kuwedzera kweEE nekuwedzera kwekudya kwekudya.Chidzidzo chapihwa muchinyorwa chino chine chinangwa chekuunza kujeka kune iyi nyaya.
Isu tinoratidza kuti muhuremu hwakajairika mbeva dzevakuru uye mbeva dzeDIO dzechirume, EE inopindirana nekupisa kwekamuri pakati pe22 ne30 ° C.Saka, EE pa22°C yaive inenge 30% yakakwirira kudarika pa30°C.mumhando dzose dzembeva.Nekudaro, musiyano wakakosha pakati pezvakajairwa uremu mbeva uye DIO mbeva ndewekuti nepo huremu mbeva dzakafanana neEE padzisiro tembiricha nekugadzirisa kudya kwekudya zvinoenderana, kudya kweDIO mbeva kwakasiyana pamatanho akasiyana.Matembiricha echidzidzo aive akafanana.Mushure memwedzi mumwechete, DIO mbeva dzakachengetwa pa 30 ° C dzakawedzera huremu hwemuviri uye huwandu hwemafuta kupfuura mbeva dzakachengetwa pa 22 ° C, nepo vanhuwo zvavo vaichengeta pane imwe tembiricha uye kwenguva imwechete yenguva havana kutungamira kupisa.zvinoenderana nekusiyana kwehuremu hwemuviri.uremu mbeva.Kuenzaniswa nematembiricha padhuze ne thermoneutral kana pakamuri tembiricha, kukura pakudziya kwekamuri kwakakonzera DIO kana akajairwa huremu mbeva pakudya kwakawanda kwemafuta asi kwete pane yakajairika uremu mbeva yekudya kuti uwane huremu hushoma.muviri.Inotsigirwa nezvimwe zvidzidzo17,18,19,20,21 asi kwete nezvose22,23.
Kukwanisa kugadzira microenvironment kuderedza kupisa kwekushisa kunofungidzirwa kuchinja kusarerekera kwekupisa kune kuruboshwe8, 12. Muchidzidzo chedu, zvose kuwedzera kwekugadzira nesting uye kuvanza kwakaderedza EE asi hazvina kukonzera kusarerekera kwekupisa kusvika ku28 ° C.Nokudaro, data yedu haitsigire kuti iyo yakaderera ye thermoneutralality mumagumbo makuru emabvi, ane kana asina dzimba dzakagadziriswa zvakatipoteredza, inofanira kuva 26-28 ° C sezvakaratidzwa8,12, asi inotsigira zvimwe zvidzidzo zvinoratidza thermoneutrality.tembiricha ye30 ° C munzvimbo yakaderera mice7, 10, 24. Kuomesa zvinhu, iyo thermoneutral point mumakonzo yakaratidza kuti haina kumira mukati mezuva sezvo yakaderera panguva yekuzorora (chiedza) chikamu, pamwe nekuda kwekuderera kwekoriori. kugadzirwa semugumisiro wekuita uye kudya-induced thermogenesis.Nokudaro, muchikamu chechiedza, nzvimbo yakaderera yekusarerekera kwekushisa inoshanduka kuva ~ 29 ° С, uye muchikamu cherima, ~ 33 ° С25.
Pakupedzisira, hukama pakati pekushisa kwe ambient uye kushandiswa kwesimba rose kunotsanangurwa nekupisa kupisa.Muchirevo chechinyorwa ichi, kuenzana kwenzvimbo kusvika kuhuwandu chinhu chakakosha chinogadzirisa chekunzwa kwekupisa, kunobata zvose kupisa kupisa (nzvimbo yepamusoro) uye chizvarwa chekupisa (vhoriyamu).Mukuwedzera kune nzvimbo yepamusoro, kupisa kwekushisa kunotsanangurwawo nekudzivirira (chiyero chekupisa kwekushisa).Muvanhu, huremu hwemafuta hunogona kuderedza kurasikirwa nekupisa nekugadzira chivharo chinodzivirira chakatenderedza ganda remuviri, uye zvave zvichitaurwa kuti mafuta akawanda akakoshawo pakupisa kwemafuta mumakonzo, kudzikisa thermoneutral point uye kudzikisa tembiricha senitivity pazasi peiyo thermal neutral point. curve slope).ambient tembiricha zvichienzaniswa neEE)12.Chidzidzo chedu chakanga chisina kugadzirwa kuti chiongorore zvakananga hukama uhwu hwekuisa nokuti data yekugadzirwa kwemuviri yakaunganidzwa mazuva 9 isati yasvika data yekushandiswa kwesimba yakaunganidzwa uye nokuti mafuta akawanda akanga asina kugadzikana mukati mekudzidza.Zvisinei, sezvo huremu hwemazuva ose uye DIO mbeva dzine 30% yakaderera EE pa 30 ° C kupfuura pa 22 ° C pasinei neine mutsauko we5-fold muhuwandu hwemafuta, data yedu haitsigire kuti kufutisa kunofanira kupa hutano hwekutanga.chinhu, zvirinani kwete mune yakaongororwa tembiricha renji.Izvi zvinoenderana nezvimwe zvidzidzo zvakagadzirirwa zviri nani kuongorora izvi4,24.Mune zvidzidzo izvi, iyo insulating mhedzisiro yekufutisa yaive diki, asi fur yakawanikwa ichipa 30-50% yehuwandu hwekupisa kupisa4,24.Nekudaro, mumakonzo akafa, kupisa kwekushisa kwakawedzera neinosvika 450% pakarepo mushure mekufa, zvichiratidza kuti iyo insulating mhedzisiro yehudzi inodiwa kuti maitiro emuviri, kusanganisira vasoconstriction, ashande.Pamusoro pemisiyano yemhando muhuto pakati pembeva nevanhu, kusasimba kwekudzivirira kufutisa mumakonzo kunogona zvakare kukanganiswa nekufunga kunotevera: Iyo inodzivirira yemafuta akawanda emunhu inonyanya kupindirana ne subcutaneous fat mass (ukobvu)26,27.Kazhinji mumakonzo Zviri pasi pe20% yemafuta emhuka yese28.Uye zvakare, yakazara mafuta marudzi anogona kunge asingambove muyero wechiSubeptimal nezvekunzwa kwemunhu, sezvo zvakakanganiswa neyakawedzera kuwanda kwenzvimbo yekuwedzera (uye nekudaro yakawedzera kurasikirwa) sekuwedzera kwemafuta kunowedzera..
Mumakonzo akajairwa uremu, kutsanya kweplasma kumazinga eTG, 3-HB, cholesterol, HDL, ALT, uye AST haina kushanduka pakudziya kwakasiyana-siyana kweanenge mavhiki e5, zvichida nokuti mbeva dzakanga dziri mumamiriro akafanana ehutano hwemagetsi.dzaive dzakafanana pakurema uye kuumbwa kwemuviri sepakupera kwechidzidzo.Zvinoenderana nekufanana kwemafuta akawanda, pakanga pasinawo misiyano mumazinga eplasma leptin, kana mukutsanya insulin, C-peptide, uye glucagon.Mamwe masaini akawanikwa muDIO mbeva.Kunyange zvazvo mbeva pa22 ° C dzakanga dzisinawo simba rakaipa rakazara munyika iyi (sezvadzaiwedzera huremu), pakupera kwechidzidzo vakange vasina simba rakawanda kana zvichienzaniswa nembeva dzakarerwa pa30 ° C, mumamiriro ezvinhu akadai se. high ketones.kugadzirwa nemuviri (3-GB) uye kuderera kwehuwandu hweglycerol uye TG muplasma.Nekudaro, misiyano inotsamira tembiricha mu lipolysis hairatidzike semhedzisiro yekuchinja kwemukati mu epididymal kana inguinal mafuta, sekuchinja kwekutaura kweadipohormone-inopindura lipase, sezvo FFA uye glycerol inoburitswa kubva mumafuta anotorwa kubva mumadhipatimendi aya ari pakati Temperature. mapoka akafanana kune rimwe nerimwe.Kunyange zvazvo tisina kuongorora manzwi ekunzwira tsitsi muchidzidzo chezvino, vamwe vakaona kuti (zvichienderana nekurova kwemwoyo uye zvinoreva arterial pressure) inofananidzwa nemhepo inopisa mumakonzo uye inenge yakaderera pa 30 ° C pane 22 ° C 20% C Nokudaro, kusiyana kwekushisa-kunoenderana nenzwi rekunzwira tsitsi kunogona kuita basa mu lipolysis mukudzidza kwedu, asi sezvo kuwedzera kwenzwi rinonzwira tsitsi kunokurudzira panzvimbo yekudzivisa lipolysis, dzimwe nzira dzinogona kurwisana nekuderera uku mumakonzo ane tsika.Inogona kuita basa mukuparara kwemafuta emuviri.Tembiricha yekamuri.Uyezve, chikamu chekusimudzira kwezwi rekunzwira tsitsi pane lipolysis inopindirana zvisina kunanga nekudzivirirwa kwakasimba kwe insulin secretion, ichiratidzira mhedzisiro ye insulin inovhiringidza kuwedzera pane lipolysis30, asi mukudzidza kwedu, kutsanya plasma insulin uye C-peptide inonzwira tsitsi toni pane tembiricha dzakasiyana. hazvina kukwana kushandura lipolysis.Pane kudaro, takaona kuti misiyano yesimba resimba ndiyo ingangove yakanyanya kupa misiyano iyi muDIO mbeva.Zvikonzero zviri pasi izvo zvinotungamira kune zvirinani kudzora kudya kwekudya neEE mune zvakajairika huremu mbeva zvinoda kumwe kudzidza.Kazhinji, zvisinei, kudya kwekudya kunodzorwa nehomeostatic uye hedonic cues31,32,33.Kunyange zvazvo pane gakava pamusoro pekuti ndeipi yezviratidzo zviviri zvakakosha zvakanyanya, 31,32,33 zvinonyatsozivikanwa kuti kushandiswa kwenguva refu kwezvokudya zvine mafuta akawanda kunotungamirira kune mamwe mafaro-akavakirwa pakudya maitiro ayo kune imwe nhanho isingaenderane. homeostasis..- yakagadziriswa kudya kwekudya34,35,36.Naizvozvo, iyo yakawedzera hedonic yekudyisa maitiro eDIO mbeva inobatwa ne45% HFD inogona kuva chimwe chezvikonzero nei mbeva idzi dzisina kuenzana kudya neEE.Sezvineiwo, misiyano yekuda kudya uye shuga yeropa-inotonga mahormone yakaonekwa zvakare mune tembiricha-inodzorwa DIO mbeva, asi kwete mune yakajairwa-huremu mbeva.MuDIO mbeva, plasma leptin mazinga akawedzera nekudziya uye mazinga eglucagon akadzikira nekupisa.Iyo tembiricha inogona kukanganisa zvakananga misiyano iyi inofanirwa kuenderera mberi nekudzidza, asi kana iri leptin, chiyero chisina kunaka chesimba uye nekudaro yakaderera mafuta mashoma mumakonzo pa22 ° C zvirokwazvo yakaita basa rakakosha, sezvo mafuta mashoma uye plasma leptin iri. yakabatana zvakanyanya37.Nekudaro, kududzirwa kwechiratidzo cheglucagon kunonyanya kunetsa.Sezvakaita insulin, secretion yeglucagon yakadziviswa zvakasimba nekuwedzera kwenzwi rekunzwira tsitsi, asi inzwi retsitsi repamusoro rakafanotaurwa kuva muboka re22 ° C, iro raiva nepamusoro-soro yeplasma glucagon concentrations.Insulin ndiyo imwe mutevedzeri wakasimba weplasma glucagon, uye insulin kudzivisa uye rudzi rwechirwere cheshuga 2 zvakanyatsobatanidzwa nekutsanya uye postprandial hyperglucagonemia 38,39.Zvisinei, DIO mbeva mukudzidza kwedu dzaivewo insulin isinganzwisisi, saka izvi zvakare zvaisagona kuva chinhu chikuru mukuwedzera kwechiratidzo cheglucagon muboka re22 ° C.Chiropa chemafuta echiropa chinobatanidzwawo zvakanaka nekuwedzera kweplasma glucagon concentration, iyo nzira iyo, iyo, inogonawo kusanganisira hepatic glucagon resistance, kuderera kwekugadzirwa kweurea, kuwedzera kutenderera kweamino acid concentrations, uye kuwedzera amino acid-yakakurudzira glucagon secretion40,41, 42.Zvisinei, sezvo zvinyorwa zvinogadziriswa zveglycerol uye TG hazvina kusiyana pakati pemapoka ekushisa mukudzidza kwedu, izvi zvakare hazvigone kuva chinhu chinokonzera kuwedzera kwehuwandu hwe plasma muboka re 22 ° C.Triiodothyronine (T3) inobata basa rakakosha muhuwandu hwemetabolism mwero uye kutanga kwekudzivirira kwemetabolism kurwisa hypothermia43,44.Nokudaro, plasma T3 concentration, zvichida inotungamirirwa nepakati pepakati nzira, 45,46 inowedzera mumakonzo uye vanhu pasi pepasi pemamiriro ezvinhu e thermoneutral47, kunyange zvazvo kuwedzera kwevanhu kuri kuduku, iyo inonyanya kufarirwa kune makonzo.Izvi zvinoenderana nekurasikirwa kwekupisa kune zvakatipoteredza.Hatina kuyera plasma T3 kuwedzera muchidzidzo chezvino, asi kuwedzera kunogona kunge kwakaderera muboka re30 ° C, iro rinogona kutsanangura kuitika kweboka iri pamazinga e plasma glucagon, sezvataka (yakagadziridzwa Mufananidzo 5a) nevamwe vakaratidza kuti T3 inowedzera plasma glucagon nenzira inoenderana nedosi.Mahomoni ethyroid anonzi anokonzera FGF21 kutaura muchiropa.Kufanana neglucagon, plasma FGF21 yakawanda yakawedzerawo ne plasma T3 concentrations (Supplementary Fig. 5b uye ref. 48), asi kana ichienzaniswa neglucagon, FGF21 plasma concentrations muchidzidzo chedu haina kukanganiswa nekushisa.Zvikonzero zvezvikonzero zvekusiyana uku zvinoda kuwedzera kudzidza, asi T3-inotungamirirwa neFGF21 induction inofanira kuitika pamatunhu akakwirira eT3 exposure kana ichienzaniswa neyakaonekwa T3-inotungamirirwa neglucagon mhinduro (Supplementary Fig. 5b).
HFD yakaratidzwa kuve yakabatana zvakanyanya nekusagadzikana kweglucose kushivirira uye insulin kushomeka (makaki) mumakonzo akarerwa pa22 ° C.Zvisinei, HFD yakanga isingabatanidzi pamwe nekukanganiswa kweglucose kushivirira kana insulin kudzivisa kana yakakura mumamiriro ekushisa (inotsanangurwa pano se 28 °C) 19.Muchidzidzo chedu, hukama uhwu hahuna kudzokororwa muDIO mbeva, asi huremu mbeva dzakachengetwa pa30 ° C dzakanyanya kuvandudza kushivirira kweglucose.Chikonzero chemusiyano uyu chinoda kuwedzera kudzidza, asi chinogona kukanganiswa nekuti DIO mbeva mukudzidza kwedu dzaive insulin isingaite, nekutsanya plasma C-peptide concentrations uye insulin concentrations 12-20 nguva dzakakwirira kupfuura dzemazuva ese uremu makonzo.uye muropa padumbu risina chinhu.glucose concentrations inosvika 10 mM (inenge 6 mM pahuremu hwemuviri), iyo inoita kunge inosiya hwindo diki kune chero mhedzisiro inobatsira yekusangana kune thermoneutral mamiriro ekuvandudza kushivirira kweglucose.Chinhu chinogona kuvhiringa ndechekuti, nekuda kwezvikonzero zvinoshanda, OGTT inoitwa pakudziya kwekamuri.Saka, mbeva dzinogara pane tembiricha dzakakwirira dzakasangana nekutonhora kutonhora, izvo zvinogona kukanganisa kutorwa kweglucose / kucheneswa.Nekudaro, zvichibva pakutsanya kwakafanana kweglucose yeropa mumapoka akasiyana etembiricha, shanduko yeambient tembiricha inogona kunge isina kukanganisa zvakanyanya mhedzisiro.
Sezvambotaurwa, ichangobva kujekeswa kuti kuwedzera tembiricha yekamuri kunogona kudzikisira mamwe maitiro kune kutonhora kushushikana, izvo zvinogona kumutsa mubvunzo kufambiswa kwegonzo data kuvanhu.Nekudaro, hazvina kujeka kuti ndeipi tembiricha yakakwana yekuchengeta mbeva kutevedzera physiology yevanhu.Mhinduro kumubvunzo uyu inogona zvakare kupesvedzerwa nendima yekudzidza uye magumo ari kudzidzwa.Muenzaniso weizvi mhedzisiro yekudya pane chiropa kuunganidzwa kwemafuta, kushivirira kweglucose uye insulin kuramba19.Panyaya yekushandiswa kwesimba, vamwe vaongorori vanotenda kuti thermoneutrality ndiyo yakanyanya tembiricha yekurera, sezvo vanhu vachingoda simba rekuwedzera kuchengetedza kupisa kwemuviri wavo, uye vanotsanangura tembiricha imwe chete yemakonzo evakuru se30 ° C7,10.Vamwe vaongorori vanotenda kuti tembiricha inofananidzwa nevanhu vanowanzosangana nemakonzo akura pabvi rimwe i23-25 ° C, sezvo vakawana thermoneutrality iri 26-28 ° C uye zvichibva pakuti vanhu vari pasi pe3 ° C.tembiricha yavo yakaderera yakaoma, inotsanangurwa pano se23°C, iri zvishoma 8.12.Chidzidzo chedu chinopindirana nezvimwe zvidzidzo zvakawanda zvinotaura kuti kusarerekera kwekupisa hakuna kuwanikwa pa26-28 ° C4, 7, 10, 11, 24, 25, zvichiratidza kuti 23-25 ° C yakaderera.Chimwe chinhu chakakosha kufunga nezve tembiricha yekamuri uye thermoneutrality mumakonzo imba imwe chete kana yeboka.Apo mbeva dzaiiswa mumapoka kwete ega, sekudzidza kwedu, kusanzwa kwetembiricha kwakaderedzwa, pamwe nekuda kwekutsvikinyidzana kwemhuka.Zvisinei, tembiricha yekamuri yakanga ichiri pasi peLTL ye25 pakashandiswa mapoka matatu.Zvichida kusiyana kwakakosha kwe interspecies munyaya iyi ndiko kukosha kwehuwandu hwebasa reBAT sekudzivirira kubva kune hypothermia.Nokudaro, nepo mbeva dzakabhadhara zvakanyanya kurasikirwa kwavo kwekoriori nekuwedzera basa reBAT, iro rinopfuura 60% EE pa5 ° C chete, 51,52 mupiro webasa reBAT revanhu kuEE wakanga wakakwirira zvikuru, muduku zvikuru.Nokudaro, kuderedza basa reBAT inogona kuva nzira inokosha yekuwedzera shanduro yevanhu.Mutemo webasa reBAT wakaoma asi kazhinji unopindirana nemigumisiro yakasanganiswa yeadrenergic stimulation, thyroid hormone uye UCP114,54,55,56,57 kutaura.Nhoroondo yedu inoratidza kuti tembiricha inoda kusimudzwa pamusoro pe27.5 ° C kana ichienzaniswa nemakonzo pa22 ° C kuitira kuti ione kusiyana kwekutaura kweBAT majini ane chekuita nebasa / activation.Zvisinei, kusiyana kwakawanikwa pakati pemapoka pa30 uye 22 ° C hakuna nguva dzose kuratidza kuwedzera kwebasa reBAT muboka re22 ° C nokuti Ucp1, Adrb2 uye Vegf-a yakaderedzwa muboka re22 ° C.Chikonzero chikuru cheiyi mibairo isingatarisirwi chichiri kuzivikanwa.Imwe mukana ndeyekuti kutaura kwavo kwakawedzera kunogona kusaratidza chiratidzo chemukamuri tembiricha yakakwira, asi mhedzisiro yekuvabvisa kubva pa30 ° C kusvika 22 ° C pazuva rekubviswa (mbeva dzakasangana ne5-10 maminetsi asati asimuka) .).
Kuganhurirwa kwechidzidzo chedu ndechekuti takangodzidza mbeva dzechirume.Imwe tsvagiridzo inoratidza kuti murume kana mukadzi anogona kuve akakosha kutariswa muzviratidzo zvedu zvekutanga, sezvo mbeva dzechikadzi dzega-mabvi dzinonyanya kudziya tembiricha nekuda kwekukwira kwekushisa kwekushisa uye kuchengetedza zvakanyanya kudzorwa zvakanyanya tembiricha.Mukuwedzera, mbeva dzechikadzi (paHFD) dzakaratidza kushamwaridzana kukuru kwesimba rekudya neEE pa30 ° C zvichienzaniswa nemakonzo echirume aidya makonzo akawanda emhando imwe chete (20 ° C munyaya iyi) 20.Nekudaro, mumakonzo echikadzi, mhedzisiro subthermonetral yemukati yakakwira, asi ine pateni yakafanana neyechirume mbeva.Muchidzidzo chedu, takatarisa kune imwechete-ibvi mbeva dzechirume, sezvo aya ari mamiriro ayo mazhinji ezvidzidzo zvemetabolism anoongorora EE anoitwa.Imwe ganhuriro yekudzidza kwedu yaive yekuti mbeva dzaive pakudya kumwe chete mukati mekudzidza, izvo zvaitadzisa kudzidza kukosha kwekamuri tembiricha yekuchinja kwemetabolism (sekuyerwa neRER shanduko yekuchinja kwekudya mune dzakasiyana macronutrient nziyo).mumakonzo echikadzi neechirume anochengetwa pa20°C zvichienzaniswa nembeva dzinoenderana dzinochengetwa pa30°C.
Mukupedzisa, kudzidza kwedu kunoratidza kuti, sezvimwe mune zvimwe zvidzidzo, lap 1 yakajairika huremu mbeva ndeye thermoneutral pamusoro peyakafanotaurwa 27.5 ° C.Pamusoro pezvo, chidzidzo chedu chinoratidza kuti kufutisa hachisi chinhu chikuru chinodzivirira mbeva dzine huremu hwakajairika kana DIO, zvichikonzera kupisa kwakafanana: EE ratios muDIO uye yakajairika huremu mbeva.Nepo kudya kwekudya kwemakonzo akajairwa kwaienderana neEE uye nokudaro kwakachengetedza huremu hwemuviri hwakagadzikana pamusoro petembiricha yese, kudya kweDIO mbeva kwaive kwakafanana pakupisa kwakasiyana, zvichikonzera chiyero chepamusoro chembeva pa30 ° C. .pa22 ° C yakawedzera uremu hwemuviri.Pakazere, zvidzidzo zvakarongeka zvinoongorora kukosha kwekugona kwekugara pasi pekushisa kwe thermoneutral zvinotenderwa nekuda kweiyo inowanzoonekwa kusashivirira pakati pembeva uye zvidzidzo zvevanhu.Semuenzaniso, muzvidzidzo zvekufutisa, tsananguro yechidimbu yekushandurwa kusingawanzo kuve yakashata inogona kunge yakakonzerwa nekuti zvidzidzo zvemurine uremu zvinowanzoitwa pamhuka dzine mwero inotonhora inodzvanywa inochengetwa pakupisa kwekamuri nekuda kwekuwedzera kweEE.Kuwedzera kuderera kwehuremu kana kuenzaniswa nehuremu hwemuviri hunotarisirwa kumunhu, kunyanya kana nzira yekuita inobva pakuwedzera EE nekuwedzera basa reBAP, iro rinonyanya kushanda uye rinoshandiswa pakupisa kwekamuri kupfuura pa30 ° C.
Maererano neDanish Animal Experimental Law (1987) uye National Institutes of Health (Publication No. 85-23) uye European Convention for the Protection of Vertebrate inoshandiswa paKuedza uye Zvimwe Zvinangwa zveSainzi (Council of Europe No. 123, Strasbourg , 1985).
Makumi maviri-vhiki ekuberekwa mbeva dzechirume C57BL/6J dzakatorwa kubva kuJanvier Saint Berthevin Cedex, France, uye dzakapihwa ad libitum standard chow (Altromin 1324) nemvura (~22°C) mushure me12:12 awa chiedza:kutenderera kwakasviba.kamuri tembiricha.Male DIO mice (mavhiki e20) akawanikwa kubva kumutengesi mumwe chete uye akapiwa ad libitum kuwana 45% kudya kwemafuta akawanda (Cat. No. D12451, Research Diet Inc., NJ, USA) uye mvura pasi pemamiriro ekurera.Mbeva dzakagadziridzwa kune zvakatipoteredza vhiki isati yatanga chidzidzo.Mazuva maviri asati aendeswa kune imwe nzira ye calorimetry system, mbeva dzakayerwa, dzakaiswa pasi peMRI scanning (EchoMRITM, TX, USA) uye dzakakamurwa kuva mapoka mana anoenderana nehuremu hwemuviri, mafuta uye huremu hwemuviri.
Dhizaini yemifananidzo yekugadzirwa kwechidzidzo inoratidzwa muMufananidzo 8. Mbeva dzakaendeswa kune yakavharwa uye tembiricha-inodzorwa indirect calorimetry system paSable Systems Internationals (Nevada, USA), iyo yaisanganisira chikafu uye mvura yemhando monitors uye Promethion BZ1 furemu yakanyorwa. mazinga ebasa nekuyera kuputika kwedanda.XYZ.Mbeva (n = 8) dzaigara dzega pa22, 25, 27.5, kana 30 ° C vachishandisa mibhedha asi pasina pekugara uye nesting material pa12:12-awa chiedza: rima cycle (chiedza: 06:00– 18:00) .2500ml / min.Makonzo akajairwa kwemazuva 7 asati anyoreswa.Zvakarekodhwa zvakaunganidzwa mazuva mana akatevedzana.Pashure pacho, mbeva dzakachengetwa pane imwe tembiricha pa25, 27.5, uye 30 ° C kwemamwe mazuva gumi nemaviri, mushure maizvozvo sero rinowedzera rakawedzerwa sezvinotsanangurwa pazasi.Zvichakadaro, mapoka emakonzo akachengetwa pa22 ° C akachengetwa pane iyi tembiricha kwemamwe mazuva maviri (kuunganidza data idzva rekutanga), uyezve tembiricha yakawedzera mumatanho e2 ° C zuva rega rega pakutanga kwechikamu chechiedza ( 06:00) kusvika yasvika 30 °C Mushure maizvozvo, tembiricha yakadzikiswa kusvika pa22°C uye data yakaunganidzwa kwemamwe mazuva maviri.Mushure memazuva maviri ekuwedzera ekurekodha pa22 ° C, matehwe akawedzerwa kumasero ose pakupisa kwose, uye kuunganidza deta kwakatanga pazuva rechipiri (zuva 17) uye kwemazuva matatu.Mushure meizvozvo (zuva rechi20), nesting material (8-10 g) yakawedzerwa kumasero ose pakutanga kwekutenderera kwechiedza (06:00) uye data yakaunganidzwa kwemamwe mazuva matatu.Nokudaro, pakupera kwechidzidzo, mbeva dzakachengetwa pa22 ° C dzakachengetwa panguva iyi tembiricha kwemazuva 21/33 uye pa22 ° C kwemazuva 8 ekupedzisira, nepo mbeva pane dzimwe tembiricha dzaichengetwa panguva iyi tembiricha kwemazuva 33./33 mazuva.Mbeva dzakadyiswa panguva yekudzidza.
Uremu hwemazuva ese uye DIO mbeva dzakatevera maitiro ekudzidza akafanana.Pazuva -9, mbeva dzakayerwa, MRI yakaongororwa, uye yakakamurwa kuva mapoka akaenzana nehuremu hwemuviri uye kuumbwa kwemuviri.Pazuva -7, mbeva dzakaendeswa kune yakavharwa tembiricha inodzorwa indirect calorimetry system yakagadzirwa neSABLE Systems International (Nevada, USA).Mbeva dzaigadzikwa dzoga nedzekurara asi dzisina matendere kana zvekuvanda.Tembiricha yakaiswa ku22, 25, 27.5 kana 30 °C.Mushure mevhiki imwe yeacclimatization (mazuva -7 kusvika ku0, mhuka dzisina kuvhiringidzika), data yakaunganidzwa pamazuva mana akatevedzana (mazuva 0-4, data inoratidzwa muFIGS. 1, 2, 5).Pashure pacho, mbeva dzakachengetwa pa25, 27.5 uye 30 ° C dzakachengetwa pasi pemamiriro enguva dzose kusvikira zuva re17th.Panguva imwecheteyo, kutonhora muboka re 22 ° C kwakawedzerwa panguva dze2 ° C zuva rimwe nerimwe nekugadzirisa kutenderera kwekushisa (06: 00 h) pakutanga kwekuvhenekera kwechiedza (data inoratidzwa muFig. 1) .Pazuva regumi nemashanu, tembiricha yakadzika kusvika 22 ° C uye mazuva maviri e data akaunganidzwa kuti ape data yekutanga yekurapa kwaitevera.Makanda akawedzerwa kune mbeva dzose pazuva regumi nenomwe, uye nesting material yakawedzerwa pazuva 20 (Fig. 5).Pazuva re23rd, makonzo akayerwa uye akaiswa pasi peMRI scanning, ndokuzosiiwa ega kwemaawa makumi maviri nemana.Pazuva 24, mbeva dzakatsanya kubva pakutanga kwephotoperiod (06:00) uye dzakagamuchira OGTT (2 g / kg) pa12: 00 (6-7 maawa ekutsanya).Pashure pacho, mbeva dzakadzoserwa kune avo vakasiyana SABLE mamiriro uye vakasunungurwa pazuva rechipiri (zuva 25).
DIO mbeva (n = 8) yakatevera iyo yakafanana protocol seyakajairika huremu mbeva (sezvinotsanangurwa pamusoro uye muFigure 8).Mbeva dzakachengeta 45% HFD mukati mekuedza kwekushandisa simba.
VO2 uye VCO2, pamwe chete nemhepo inopisa yemvura, yakanyorwa pane imwe nguva ye1 Hz ine nguva yesero ye 2.5 min.Chikafu uye kutora kwemvura kwakaunganidzwa nekuramba kuchirekodhwa (1 Hz) yehuremu hwezvikafu uye mvura pails.Iyo yemhando yepamusoro yakashandiswa yakashuma kugadzirisa kwe0.002 g.Manhanho ekuita akarekodhwa pachishandiswa 3D XYZ beam array monitor, data yakaunganidzwa pachigadziro chemukati che240 Hz uye yakashuma sekondi yega yega kuti iverenge nhambwe yese yafambwa (m) ine chigadziriso chinoshanda che 0.25 cm.Iyo data yakagadziriswa neSable Systems Macro Interpreter v.2.41, kuverenga EE neRER uye kusefa kunze kunze (semuenzaniso, zviitiko zvekudya zvenhema).Iyo macro muturikiri inogadziriswa kuti ibudise data kune ese ma paramita maminetsi mashanu ega ega.
Pamusoro pekutonga EE, ambient tembiricha inogonawo kudzora zvimwe zvikamu zvemetabolism, kusanganisira postprandial glucose metabolism, nekugadzirisa secretion yeglucose-metabolizing mahormone.Kuti tiedze iyi hypothesis, takazopedza kudzidza tembiricha yemuviri nekudenha mbeva dzinorema neDIO oral glucose load (2 g/kg).Nzira dzinotsanangurwa zvakadzama mune zvimwe zvinhu.
Pakupera kwechidzidzo (zuva 25), mbeva dzakatsanya kwemaawa 2-3 (kutanga pa06: 00), anesthetized ne isoflurane, uye yakanyatsobuda ropa ne retroorbital venipuncture.Quantification yeplasma lipids uye mahormone uye lipids muchiropa inotsanangurwa muSupplementary Materials.
Kuti uongorore kana tembiricha yegomba ichikonzera shanduko yemukati mune adipose tishu inokanganisa lipolysis, inguinal uye epididymal adipose tishu yakabviswa zvakananga kubva kumakonzo mushure mechikamu chekupedzisira chekubuda ropa.Matishu akagadziriswa achishandisa ichangobva kugadzirwa ex vivo lipolysis assay inotsanangurwa muSupplementary Methods.
Brown adipose tissue (BAT) yakaunganidzwa pazuva rekupera kwechidzidzo uye yakagadziriswa sezvinotsanangurwa mukuwedzera nzira.
Data inoratidzwa sezvinoreva ± SEM.Magirafu akagadzirwa muGraphPad Prism 9 (La Jolla, CA) uye magirafu akagadziridzwa muAdobe Illustrator (Adobe Systems Incorporated, San Jose, CA).Kukosha kwenhamba kwakaongororwa muGraphPad Prism uye yakaedzwa neaviri-t-bvunzo, yakadzokororwa nhanho imwe-nzira/mbiri-nzira ANOVA inoteverwa neTukey's akawanda kuenzanisa bvunzo, kana isina pairing nzira imwe ANOVA inoteverwa neTukey's akawanda kuenzanisa bvunzo sezvinodiwa.Kugoverwa kweGaussian kwedata kwakasimbiswa neiyo D'Agostino-Pearson normality bvunzo isati yaedzwa.Saizi yemuenzaniso inoratidzwa muchikamu chinoenderana che "Results" chikamu, pamwe chete nengano.Kudzokorora kunotsanangurwa sechipimo chipi nechipi chinotorwa pamhuka imwe chete (mu vivo kana pamuenzaniso wenyama).Nezve data reproducibility, mubatanidzwa pakati pekushandisa simba uye tembiricha yekesi yakaratidzwa muzvidzidzo zvina zvakazvimiririra vachishandisa mbeva dzakasiyana dzine dhizaini yekudzidza yakafanana.
Detailed experimental protocols, materials, and raw data is available on a reasonable request from an lead author Rune E. Kuhre.Ichi chidzidzo hachina kugadzira matsva akasiyana reagents, transgenic mhuka / masero mitsara, kana kuteedzera data.
Kuti uwane rumwe ruzivo nezve dhizaini yekudzidza, ona Nature Research Report abstract yakabatana nechinyorwa ichi.
Yese data inoumba girafu.1-7 yakaiswa muSainzi dhatabhesi repository, nhamba yekupinda: 1253.11.sciencedb.02284 kana https://doi.org/10.57760/sciencedb.02284.Iyo data inoratidzwa muESM inogona kutumirwa kuRune E Kuhre mushure mekuedzwa kwakanaka.
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Nguva yekutumira: Oct-28-2022
